The hows and whys of aerobic H2 metabolism

The bacterial [NiFe]-hydrogenases have been classified as either ‘standard’ or ‘O2-tolerant’ based on their ability to function in the presence of O2. Typically, these enzymes contain four redox-active metal centers: a Ni–Fe–CO–2CN− active site and three electron-transferring Fe–S clusters. Recent research suggests that, rather than differences at the catalytic active site, it is a novel Fe–S cluster electron transfer (ET) relay that controls how [NiFe]-hydrogenases recover from O2 attack. In light of recent structural data and mutagenic studies this article reviews the molecular mechanism of O2-tolerance in [NiFe]-hydrogenases and discusses the biosynthesis of the unique Fe–S relay.

► A novel Fe–S cluster controls how [NiFe]-hydrogenases recover from O2 attack. ► Molecular mechanism of O2-tolerance. ► Biosynthesis of the unique Fe–S relay.